Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

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Ressource 1Download: s41421-018-0014-5.pdf (3545.31 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_2F8C4A54B142
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.
Journal
Cell discovery
Author(s)
Sng M.K., Chan JSK, Teo Z., Phua T., Tan EHP, Wee JWK, Koh NJN, Tan C.K., Chen J.P., Pal M., Tong BMK, Tnay Y.L., Ng X.R., Zhu P., Chiba S., Wang X., Wahli W., Tan N.S.
ISSN
2056-5968 (Print)
ISSN-L
2056-5968
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
4
Pages
15
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre- <i>Pparb/d</i> <sup>-/-</sup> ) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 ( <i>Lrg1</i> ), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of <i>Lrg1</i> by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre- <i>Pparb/d</i> <sup>-/-</sup> mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis.

Pubmed
Web of science
Open Access
Yes
Create date
14/04/2018 11:01
Last modification date
20/08/2019 13:14
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